Biliary secretion of trace elements and minerals in the rat: Effects of bile flow variation and diurnal rhythms

Abstract

Effects of bile flow variations on bile secretion of trace elements were systematically evaluated by Proton-Induced X-ray Emission (PIXE) in the unanesthetized rat: (i) longitudinally for a 9 day-period of bile drainage, (ii) continuously for a period of 24 h, to include circadian rhythm and (iii) during exogenous bile salt administration. Potassium and Ca were determined for comparative purposes. In rat bile, six trace elements could always be detected by PIXE (Fe, Zn, Cu, Mo, Mn, Br); occasionally some V, Cr, Sr and Pb was found. Se could not be detected in bile. Bile-plasma concentration ratios of the elements could arbitrarily be divided into three groups: Fe, Zn and Se < 1; Ca, K, Cu, Mo and Br approx. 1 and Mn ⪢1. After interruption of the enterohepatic circulation, bile flow and bile salt concentration dropped sharply within 4 h to 36% and 4% of their initial values, respectively. Output rates of K, Ca, Mo, Br, Zn and Fe closely followed the decrease in bile flow; bile secretion of Mn and Cu, on the other hand, was minimally affected. A circadian rhythm was observed for all detectable elements; during the night period, secretion rates of Zn, Fe, Ca and K increased maximally by 60–80% and that of Mn, Mo, Br and Cu by 30–50%. Bile salt output and bile flow increased maximally by 70% and 50%, respectively, in the same time interval. Infusion (106 μmol/h) of taurocholate (TC), a micelle forming bile salt or dehydrocholate (DHC), a non-micellar bile salt, caused a maximal increase in bile flow by 67% and 93%, respectively. Under these conditions, biliary secretion of K, Ca, Mo, Br and Fe were stimulated by both types of bile salts, almost to a similar extent as bile flow. In contrast, the secretion of Zn, Cu and Mn was not affected or even reduced. This study shows that most detectable endogenous trace elements show a strong bile flow-dependency in their biliary secretion, except Zn, Cu and Mn. The elimination of Cu and Mn via bile, which represents the main route for their removal from the body, is largely independent of acute changes in bile flow, but does show a marked circadian rhythm.